The Mass Spectrometry Facility at the University of California San Diego wishes to acquire an Applied Biosystems 4700 Matrix-assisted laser desorption ionization (MALDI) tandem time-of-flight (TOF-TOF) mass spectrometer. This mass spectrometer has novel patented tandem sources in which collision-induced dissociation occurs from the high-energy (1-2 keV) singly charged parent ions generated by MALDI. This technology is critical for determining the protein functional landscape, the next step after completion of the human genome project. The genome sequence revealed many fewer proteins than expected, suggesting that proteins have multiple states with differing functions. Protein function can be altered by participation in multiprotein complexes, post-translational modification state, and these modifications can result in different conformational states. The MALDI-TOF-TOF instrument will be used to approach all three of these questions. First, we will identify proteins in complexes in a robust and comprehensive way, even when the genome sequences of the organism from which the complex was isolated are not available. Second, we will identify the post-translational modifications on each of the proteins in the complex, beginning with glycosylation and phosphorylation. Third, we will identify the individual amino acids on surfaces of the proteins that interact in the complex, and understand the conformational changes that accompany binding. Professors H. Zhou, J. Dixon, S. Taylor, R. Tsien, B. Tebo, and P. van der Geer are engaged in development of proteomics experiments to identify proteins in cellular complexes. Professors Zhou and P. Taylor are studying phosphorylation, glycosylation, and modification of proteins by environmental agents. Professor E. Komives pioneered the use of MALDI amide H/2H exchange for identification of protein interfaces and conformational changes that accompany protein-protein interactions. For this project, the MALDI-TOF-TOF will enable measurements of amide deuteration down to the single amino acid level.